Cone Threshold Research Articles

Do question phrasing and long wavelength cone sensitivity influence red cap test responses in healthy patients?

This study investigates the influence of question phrasing and long wavelength cone sensitivity on red cap test responses in healthy patients. A chart review of 230 adult patients assessed responses to two different phrasings of the red cap test. Phrasing 1 asked the patient to describe the left eye relative to the right while Phrasing 2 asked the patient to name the brighter eye and provided an option for the patient to report no difference. Long wavelength cone thresholds were measured using the Konan CCT. Across both phrasings, 33 % of patients reported red saturation asymmetry, with a significant difference in positive responses between the two phrasings (43.6 % for Phrasing 1 vs. 11.3 % for Phrasing 2, (χ2 = 121.694, p <.001). No significant interocular differences in long wavelength cone sensitivity were found in those patients with a positive red cap response. Phrasing contributes to the high false positive rate of the red cap test reported in healthy patients.

Mechanisms of cone sensitivity loss in retinitis pigmentosa.

To explore the mechanisms of cone sensitivity loss in retinitis pigmentosa by combining two-colour perimetry with threshold versus intensity (tvi) testing. Seven subjects with autosomal recessive retinitis pigmentosa and 10 normal subjects were recruited and underwent perimetric testing of one eye using 480- and 640-nm Goldman size V targets presented under scotopic conditions (no background illumination) and against a white background ranging in luminance from -1.5 to 2 log cd m-2 in 0.5 log cd m-2 steps. Data were fitted with tvi functions of the form logT = logT0 + log ((A + A0)/A0)n, where T is the threshold, T0 is the absolute threshold, A is the background intensity, A0 is the 'dark-light' constant and n is a gain constant. Reliable tvi functions could not be obtained within the region of the visual field corresponding to loss of the ellipsoid zone on optical coherence tomography. At fixation, changes in both T0 and A0 were observed, consistent with a d1 mechanism loss, which resulted in an upwards and rightwards shift of the tvi function. Losses at [±3°, ±3°] demonstrated changes in T0, consistent with a d3 mechanism loss, resulting in an upwards translation of the tvi curve. Although the absolute cone threshold was elevated at each location, shifts in the tvi function (so-called d1 mechanism loss) at fixation minimise threshold elevation in the presence of white adapting backgrounds, such as those typically employed in standard two-colour perimetry. At more peripheral testing locations, changes in threshold occurred independent of background luminance (so-called d3 mechanism loss). These findings suggest that backgrounds which selectively adapt rods while maintaining cones at, or near, absolute threshold may be preferable to conventional two-colour perimetry for assessing loss of cone sensitivity, especially at the point of fixation.

Establishing Fully-Automated Fundus-Controlled Dark Adaptometry: A Validation and Retest-Reliability Study.

The purpose of this study was to establish and validate a novel fundus-controlled dark-adaptometry method. We developed a custom dark-adaptometry software for the S-MAIA device using the open-perimetry-interface. In the validation-substudy, participants underwent dark-adaptometry testing with a comparator device (MonCvONE, 59% rhodopsin bleach, cyan and red stimuli centered at 2 degrees, 4 degrees, and 6 degrees eccentricity). Following a brief break (approximately 5 minutes), the participants were bleached again and underwent dark-adaptometry testing with the S-MAIA device (same loci). In the retest reliability-substudy, participants were tested twice with the S-MAIA device (same loci as above). Nonlinear curve fitting was applied to extract dark-adaptation curve parameters. Validity and repeatability were summarized in terms of the mean bias and 95% limits of agreement (LoAs). In the validation-substudy (N = 20 participants, median age interquartile range [IQR] 31.5 years [IQR = 25.8, 62.0]), measures of rod-mediated dark-adaptation showed little to no between method differences for the cone-rod-break-time (bias 95% confidence interval [95% CI] of +0.1 minutes [95% CI = -0.6 to 0.8]), rod-intercept-time (-0.23 minutes [95% CI = -1.38 to 0.93]), and S2 slope (-0.01 LogUnits/minutes [95% CI = -0.02 to -0.01]). In the retest reliability-substudy (N = 10 participants, 32.0 years [95% CI = 27.0, 57.5]), the corresponding LoAs were (cone-rod-break-time) -3.94 to 2.78 minutes, (rod-intercept-time) -4.55 to 3.11 minutes, and (S2 slope [rate-limited component of rod recovery]) -0.03 to 0.03 LogUnits/minutes. The LoAs for the steady-state cone and rod thresholds were -0.28 to 0.33 LogUnits and -0.34 to 0.28 LogUnits. The devised fundus-controlled dark-adaptometry method yields valid and reliable results. Fundus-controlled dark-adaptometry solves the critical need for localized testing of the visual cycle and retinoid transfer in eyes with unstable fixation.

LOW-DOSE SUPPLEMENTATION WITH RETINOL IMPROVES RETINAL FUNCTION IN EYES WITH AGE-RELATED MACULAR DEGENERATION BUT WITHOUT RETICULAR PSEUDODRUSEN.

The aim of this study was to determine the functional impact of oral vitamin A supplementation in patients with intermediate age-related macular degeneration with and without reticular pseudodrusen (RPD) demonstrating dysfunction in dark adaptation. Five patients with intermediate age-related macular degeneration and without RPD (AMD group; mean ± SD age 78.0 ± 4.7 years) and seven with RPD (RPD group; age 74.1 ± 11.2 years) were supplemented with 16,000 IU of vitamin A palmitate for 8 weeks. Assessment at baseline, 4, 8, and 12 weeks included scotopic thresholds, dark adaptation, best-corrected and low luminance visual acuities, and the low-luminance quality of life questionnaire. In the linear mixed model, rod intercept time improved significantly in the AMD group (mean [95% CI] change -1.1 minutes [-1.8; -0.5] after 4 weeks ( P < 0.001) and -2.2 min [-2.9 to -1.6] after 8 weeks of vitamin A supplementation ( P < 0.001). The dark adaptation cone plateau also significantly improved (i.e., more sensitive cone threshold) at 4 and 8 weeks ( P = 0.026 and P = 0.001). No other parameters improved in the AMD group, and there was no significant improvement in any parameter in the RPD group despite significantly elevated serum vitamin A levels measurable in both groups after supplementation ( P = 0.024 and P = 0.013). Supplementation with 16,000 IU vitamin A, a lower dose than used in previous studies, partially overcomes the pathophysiologic functional changes in AMD eyes. The lack of improvement in the RPD group may indicate structural impediments to increasing vitamin A availability in these patients and/or may reflect the higher variability observed in the functional parameters for this group.

Rod and Cone Dark Adaptation in Congenital Aniridia and Its Association With Retinal Structure.

To characterize the association between dark-adapted rod and cone sensitivity and retinal structure in PAX6-related aniridia. Dark-adaptation curves were measured after a 5-minute exposure to bright light with red (625 nm) and green (527 nm) 2° circular light stimuli presented at ≈20° temporal retinal eccentricity in 27 participants with aniridia (nine males; 11-66 years old) and 38 age-matched healthy controls. A two-stage exponential model was fitted to each participant's responses to determine their cone and rod thresholds over time. The thicknesses of macular inner and outer retinal layers were obtained from optical coherence tomography images in 20 patients with aniridia and the 38 healthy controls. Aniridia-associated keratopathy (AAK) grade (0-3) and lens opacities were quantified by clinical examination of the anterior segment. The rod-cone break time was similar between patients with aniridia and healthy controls. Dark-adapted cone and the rod thresholds were higher in aniridia compared with healthy controls. In aniridia, foveal outer retinal layer thickness correlated with both final cone and rod thresholds. A multiple regression model indicated that foveal outer retinal layer thickness and age were the main explanatory variables to predict both final cone and rod thresholds in aniridia when the AAK grade was 2 or less. The results show that both rod- and cone-related functions are affected in PAX6-related aniridia and suggest that retinal anatomical and physiological changes extend beyond the area commonly studied in this condition: the central macula.

The value of colour assessment in diagnostic dilemmas

AbstractBackground: When the goal of clinical assessment is to segment, divide, and classify cases into neat discrete boxes it can often be frustrating to encounter cases which do not fit standard diagnosis algorithms. However, such diagnostic dilemmas often provide a valuable insight into the boundaries of current clinical procedures and the potential value psychophysical assessment can provide when used in conjunction with standard diagnosis algorithms. We present such a case involving localized retinal dysfunction that is not fully consistent with signs of either autoimmune retinopathy or occult maculopathy.Methods: Specific visual function loss was investigated in a health 32‐year‐old male with suspected localized retinal dysfunction, affecting the central retina. Blood tests and electro‐diagnostics were carried out after the patient presented with acute onset ‘foggy’ central vision. The working diagnosis from this initial visit was autoimmune retinopathy and oral steroids were prescribed. Following no change in symptoms a year after initially presenting, the patient was referred to City, University of London for bespoke assessments of specific visual functions. These included assessments of central and peripheral red / green (RG) and yellow / blue (YB) colour vision, mesopic visual acuity (VA), functional contrast sensitivity (FCS), rod‐ and cone‐mediated flicker sensitivity, and pupil responses measured using both rod‐ and cone‐enhanced stimuli.Results: The loss of vision affected primarily the central 20° with a mean VA of 6/36 in each eye. Fundus images, fluorescein angiography, and full field electroretinograms (ERGs) were normal, but pattern and focal ERGs were undetectable indicating localized dysfunction in central vision with OCT images showing a disrupted ellipsoid zone in each eye. The patient's mean corpuscular volume was 69 femtoliters, with red cell indices suggestive of thalassemia. Testing at City, University of London confirmed a loss of VA and FCS in the central 10° field, although both VA and FCS depended strongly on light level and were less affected with negative contrast stimuli. A loss of RG and YB colour vision was also measured centrally. Outside the central 10° field EA had almost normal colour and spatial vision. Rod‐ and cone‐mediated, flicker thresholds were elevated, with cone thresholds 10‐fold higher than normal. Pre‐stimulus pupil size, constriction amplitudes and latencies were normal with both centrally presented and peripheral stimuli.Conclusions: Psychophysical measurements in a patient with presumed autoimmune maculopathy showed atypical macular dysfunction that appears to preferentially affect negative contrast stimuli. Despite damage to the retinal mechanisms involved in spatial vision and light adaptation pupil responses remained unaffected. This unusual case highlights the importance of detailed phenotyping in understanding unknown aetiology.

Genetic elimination of rod/cone coupling reveals the contribution of the secondary rod pathway to the retinal output.

In the retina, signals originating from rod and cone photoreceptors can reach retinal ganglion cells (RGCs)-the output neurons-through different pathways. However, little is known about the exact sensitivities and operating ranges of these pathways. Previously, we created rod- or cone-specific Cx36 knockout (KO) mouse lines. Both lines are deficient in rod/cone electrical coupling and therefore provide a way to selectively remove the secondary rod pathway. We measured the threshold of the primary rod pathway in RGCs of wild-type mice. Under pharmacological blockade of the primary rod pathway, the threshold was elevated. This secondary component was removed in the Cx36 KOs to unmask the threshold of the third rod pathway, still below cone threshold. In turn, the cone threshold was estimated by several independent methods. Our work defines the functionality of the secondary rod pathway and describes an additive contribution of the different pathways to the retinal output.

IMPAIRMENTS IN CONE PIGMENT REGENERATION AND ABSOLUTE THRESHOLD IN MACULAR TELANGIECTASIA TYPE 2.

To test the hypothesis that Müller cell dysfunction in macular telangiectasia type 2 (MacTel) results in delayed cone adaptation kinetics and to assess absolute cone and rod thresholds in this condition. Adaptation after an approximate 63.5% full-field cone photopigment bleach was assessed for Goldmann size V (1.7° diameter) 640 nm (red) and 480 nm (blue) targets presented at a retinal locus corresponding to 2° temporal to fixation. The cone time constant of adaptation and absolute cone and rod thresholds were calculated from exponential functions fitted to the resultant dark adaptation curves. Eighteen eyes with MacTel (from 11 patients) were compared with 19 control eyes (from 16 normal subjects). Cone adaptation kinetics were significantly impaired in MacTel, as was the absolute cone threshold. Final thresholds for blue targets were also significantly elevated in MacTel, consistent with impaired rod absolute threshold. Losses in sensitivity observed in MacTel were consistent with a so-called d1/2 mechanism (i.e., receptoral) site of sensitivity loss. In addition to previously documented impairments in rod dark adaptation, MacTel results in a significant elevation in cone thresholds because of pathology at the level of the photoreceptors. The delays in cone adaptation that we found in eyes with MacTel may reflect impairment of the Müller cell-mediated cone-specific visual cycle.

Correlations Between Dark-Adapted Rod Threshold Elevations and ERG Response Deficits in Duchenne Muscular Dystrophy.

PurposeThe purpose of this study was to characterize changes in the full-field flash electroretinogram (ERG) in association with psychophysical dark-adapted visual thresholds in patients with genetically characterized Duchenne muscular dystrophy (DMD) either lacking Dp427 (Up 30) or at least Dp260 in addition to Dp427 (Down 30).MethodsTwenty-one patients with DMD and 27 age-similar controls participated in this study. Dark-adapted (0.01, 3.0, and 10 cd.s/m² flashes) and light-adapted (3.0 cd.s/m² flash) ERGs were recorded following International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. Visual detection thresholds to 625-nm (cone function) and 527-nm (rod function) light-emitting diode (LED) flashes (2 degree diameter) were measured during a dark adaptation period after a 1-minute exposure to a bleaching light (3000 cd/m²). Initially, 8 minutes of interleaved 625-nm and 527-nm thresholds were measured. After an additional 5 minutes of dark-adaptation, a second set of threshold measurements to 527-nm stimuli was performed during the subsequent 6 minutes.ResultsDark-adapted b-wave amplitude was significantly reduced to all strengths of flash and a-wave in response to the strong flash stimulus was delayed (15.6 vs. 14.7 ms, P < 0.05) in patients with Down 30 compared with controls. Dark-adapted cone thresholds did not differ among the groups (−2.0, −1.8, and −1.7 log cd/m² for Down 30, Up 30, and controls, respectively, P = 0.21). In contrast, dark-adapted rod thresholds were elevated (F(2,36) = 8.537, P = 0.001) in patients with Down 30 (mean = −3.2 ± 1.1 log cd/m²) relative to controls (mean = −4.2 ± 0.3 log cd/m²). Dark-adapted b-wave amplitudes were correlated with dark-adapted rod sensitivity in patients with DMD (Spearman Rho = 0.943, P = 0.005). The changes were much smaller or absent in patients with intact Dp260.ConclusionsDp260 is particularly required for normal rod-system function in dark adaptation.

Age-related change in flicker thresholds with rod- and cone-enhanced stimuli.

PurposeRod and cone photoreceptor-specific tests can be time-consuming. A new non-invasive test is described. The test is based on the measurement of flicker modulation thresholds with rod- and cone-enhanced visual stimuli, which requires only minimum adaptation time. Here, we investigated how the rod-and cone-mediated flicker thresholds vary with age.MethodsMonocular thresholds with rod and cone–enhanced stimuli were measured in 140 healthy adults, (age range: 18–75 years), foveally (0°) and at four parafoveal locations, at an eccentricity of 5° in each of the four quadrants using five, adaptive, interleaved staircases. Temporal frequencies, stimulus sizes, background luminance and spectral composition, were adjusted appropriately to achieve approximately 1 log unit separation in sensitivity between the rod- and cone-enhanced stimuli. Spectrally calibrated, ‘neutral density’ filters were used to enable adequate control of display luminance for rod enhanced stimuli.ResultsThe magnitude of central and parafoveal rod thresholds was significantly higher than the central and parafoveal cone thresholds, respectively (p < 0.001) in both the age groups. However, the rate of increase in central rod thresholds (y = 0.45x—12.79; linear regression equation) was not significantly steeper than the rate of increase in central (y = 0.29x—8.53) cone thresholds (p = 0.15). Centrally, cone thresholds showed a better correlation with rod central thresholds for the age > 45 years (Spearman correlation, ρ = 0.74, p < 0.001) compared to age ≤ 45 years (ρ = 0.41, p < 0.001).ConclusionsThresholds with rod- and cone-enhanced stimuli are largely invariant below 45 years of age and increase rapidly above this age. This age-wise normative database can be used as an effective functional-marker to assess photoreceptor sensitivities in retinal diseases.

Repeatability of Scotopic Sensitivity and Dark Adaptation Using a Medmont Dark-Adapted Chromatic Perimeter in Age-related Macular Degeneration.

PurposeFunctional studies of rods in age-related macular degeneration using the Medmont Dark-Adapted Chromatic Perimeter (DACP) have demonstrated impairments in scotopic sensitivities and dark adaptation (DA). We investigated the intersession repeatability of scotopic sensitivity and DA parameters including the rod intercept time recorded from the Medmont DACP.MethodsScotopic thresholds (14 test points) and DA using a 30% photobleach (eight test points) were measured on two separate days from participants 50 years of age or older with a range of age-related macular degeneration severity at loci superior and inferior to the fovea. Repeatability coefficients were calculated for prebleach scotopic sensitivity, and for DA parameters including rod intercept time.ResultsTwelve participants (mean age, 79.7 ± 8.1 years) repeated Medmont DACP testing within 50 days. Repeatability coefficients for prebleach scotopic sensitivity to long wavelength (red, 625 nm) and short wavelength (cyan, 505 nm) were 5.9 dB and 7.2 dB, respectively. The DA curve-derived repeatability coefficients for cone threshold was 3.9 dB, final threshold 5.3 dB, with an R value of 0.075 decades/min, rod intercept time 7.6 minutes, and RITslope 0.54 min/degree.ConclusionsThis study establishes repeatability coefficients for scotopic thresholds and multiple DA parameters obtained with the Medmont DACP in patients with age-related macular degeneration. These repeatability coefficients will serve as the basis for determining clinically meaningful change in rod function in future clinical trials.Translational RelevanceMeasures of repeatability parameters of scotopic thresholds and DA are essential to the accurate interpretation of results in future studies and trials using these measures.

The Light and the Dark of Early and Intermediate AMD: Cone- and Rod-Mediated Changes Are Linked to Fundus Photograph and FAF Abnormalities.

The purpose of this paper is to describe the extent to which scotopic and photopic measures of visual function predict color fundus photograph (CFP) and fundus autofluorescence (FAF) changes in early and intermediate nonexudative AMD. Sixty-nine observers were recruited: 56 AMD patients (mean age, 73 ± 12.98 years) and 13 controls (mean age, 67.77 ± 9.72 years). A nonmydriatic retinal camera was used to obtain stereo fundus photographs and FAF images were recorded with a cSLO Heidelberg Spectralis HRA+OCT. Visual acuity (VA) was measured using an Early Treatment of Diabetic Retinopathy Study chart. Contrast sensitivity (CS) was assessed with a Pelli-Robson chart. Dark adaptation (DA) curves were recorded at 3° eccentricity using a PC-based technique. Analysis of these curves yielded five parameters: cone threshold (CT), cone time constant (CC), cone-rod break (α), slope of the second rod component (S2), and rod-rod break (β). Both cone and rod sensitivity recovery were grossly abnormal in the patients. The rod recovery slope (S2) most accurately predicted the fundus photograph-based grade and the FAF classification (ρ = 0.61 and ρ = 0.60, respectively; both P < 0.0001). CS showed a strong association with FAF (ρ = 0.50, P < 0.0001) and with fundus photograph-based grade (ρ = 0.38, P < 0.002). There was no correlation between VA and either imaging method. Dynamic, rod-based measures most accurately reflect the severity of early AMD. Although less specific to AMD than DA changes, static photopic abnormalities such as CS also correspond with morphologic changes. Assessment of function in early AMD should include dynamic rod- and cone-mediated measurements of sensitivity recovery.

Age‐related changes in flicker sensitivity with rod‐ and cone‐enhanced stimuli

AbstractPurposeCone and rod photoreceptors are usually isolated using high light levels for cone vision and full dark‐adaptation, when only rods respond to light. Such methods are not ideal for clinical use. A new rod/cone flicker test has been designed to isolate and measure rod‐ and cone‐mediated signals in the absence of colour signals with one minute adaptation.Methods118 healthy adults (Mean age ± standard deviation: 40 ± 15 years), were investigated. None of the participants had a history of or exhibited signs of ocular disease. Rod and cone thresholds were measured monocularly in central vision and in each of the four quadrants (superonasal, superotemporal, inferonasal and inferotemporal) at an eccentricity of 5°. Temporal frequencies, stimulus sizes, background luminances and spectral composition were adjusted appropriately to achieve approximately equal thresholds with ~ 10‐fold separation in sensitivity between the rod‐ and cone‐enhanced stimuli. Flicker thresholds were measured using five adaptive (two‐down, one‐up), interleaved staircases. Spectrally calibrated, ‘neutral density’ glasses were used to enable adequate control of display luminance at low levels.ResultsThe superotemporal quadrant had the lowest mean rod and cone thresholds compared to other tested quadrants. For participants, above 50 years of age, the central rod thresholds increased 0.53% per year, whereas cone thresholds increased 0.29% per year and this decline was faster than other respective quadrants. Overall, among the locations tested, the central rod (ρ = 0.547; p &lt; 0.005) and cone (ρ = 0.504, p &lt; 0.005) thresholds demonstrated the strongest correlation with age.ConclusionsThe new test isolates rod and cone signals sufficiently well to detect selective loss of photoreceptor function in normal ageing. The potential use of rod‐ and cone‐enhanced tests in patients with selective loss of photoreceptors and other retinal diseases (e.g., AMD, glaucoma, diabetes) remains to be explored.

Slowed Dark Adaptation in Early AMD: Dual Stimulus Reveals Scotopic and Photopic Abnormalities.

The recovery of visual sensitivity after a photobleach in early AMD is slowed in rods but cones also may be abnormal. The purpose of this article was to test different stimulus locations to investigate cone function and its relation to rod abnormalities. Stimuli were presented at two locations, 3.0° and 5.5°, in the inferior visual field. Post photobleach dark adaptation (DA) curves from 50 early-AMD patients were compared with those from 15 healthy controls of similar age. Curves were characterized in terms of four parameters: ct, cone threshold; α, the transition point from cone to rod function; S2, the slope of the second rod-mediated component; and β, the transition from the second to the third rod-mediated component. There were strong location effects for the healthy group and the AMD group. Cone threshold was higher for the outer compared with the inner stimulus (P = 0.001), S2 was steeper for outer compared with inner (P < 0.001), α was shorter for outer (P = 0.004), and β was shorter for outer than inner (P = 0.002). The high variance in the patient data, particularly for α and β, explained the absence of a group*location interaction in the statistics. The data provide a novel perspective on abnormal cone- and rod-sensitivity recovery in early dry AMD. The comparison of pairs of DA curves from different locations highlights the involvement of cones in the underlying pathology of AMD. Dynamic measures of visual function are particularly sensitive to early AMD.

Cone photoreceptor macular function and recovery after photostress in early non-exudative age-related macular degeneration.

PurposeTo identify parameters from cone function and recovery after photostress that detect functional deficits in early non-exudative age-related macular degeneration (AMD) and to determine the repeatability of these parameters.MethodsCone-mediated visual function recovery after photostress was examined in three groups of subjects: young normal subjects (ages 20–29; N=8), older normal subjects (ages 50–90; N=9), and early non-exudative AMD subjects (ages 50–90; N=12). Eight AMD and four normal subjects were retested 1 year after the initial evaluation. Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) and parameters of cone function (baseline cone sensitivity and cone recovery half-life following photobleach) were measured and compared between AMD and normal subjects. Short-term repeatability was assessed for each subject’s initial evaluation. Long-term repeatability was assessed by comparing outcomes from the initial evaluation and 1-year follow-up.ResultsThe mean baseline cone threshold was significantly worse in subjects with early AMD compared to older normal subjects (−1.80±0.04 vs −1.57±0.06 log cd/m2 p=0.0027). Moreover, the baseline cone threshold parameter exhibited good short-term (intraclass correlation coefficient [ICC]=0.88) and long-term (ICC=0.85) repeatability in all subjects. The cone intercept parameter and ETDRS VA were not significantly different between AMD and older normal subject groups. Cone recovery half-life was significantly different between older normal and AMD subject groups (p=0.041). Neither ETDRS VA nor cone function parameters were significantly different for any group at the 1-year follow-up.ConclusionThe baseline cone threshold shows potential as a novel parameter to assess visual dysfunction in early AMD. This outcome consistently detected deficits in AMD subjects, and differentiated them from age-matched controls with high test–retest repeatability.

Foraging patterns of common crossbills (Loxia curvirostra) on spruces (Picea spp.) in Scotland

Common crossbills forage on Sitka spruce and Norway spruce when the cones reach full size in late summer until the seeds have shed in the following spring. Sitka spruce start shedding seed in autumn, thereby reducing the food supply for crossbills through autumn to spring, whereas Norway spruce retain their seeds until spring. Crossbills forage on cones that are attached to the tree (more so for Norway spruces) or are removed from the tree by the crossbills before feeding. The latter cones are then dropped after seed extraction. The mean length of dropped Sitka spruce cones was 72 mm, close to the average length in a widespread survey. This suggests little size selection. The mean length of dropped Norway spruce cones was 90 mm, which was much smaller than the average length in the survey. Although used, large cones are probably left attached to trees because they are too heavy to handle if cut from the tree. The average percentage of seeds extracted before a cone was dropped was 45% for Sitka spruce and 42% for Norway spruce. There was a trend for fewer Sitka spruce seeds to be taken per cone across the period between autumn and spring. Incomplete extraction of seeds suggests that cones become unprofitable as the seed number is depleted in cones and that the threshold for switching cones changes as the number of seeds per cone declines.

Spatiochromatic Interactions between Individual Cone Photoreceptors in the Human Retina.

A remarkable feature of human vision is that the retina and brain have evolved circuitry to extract useful spatial and spectral information from signals originating in a photoreceptor mosaic with trichromatic constituents that vary widely in their relative numbers and local spatial configurations. A critical early transformation applied to cone signals is horizontal-cell-mediated lateral inhibition, which imparts a spatially antagonistic surround to individual cone receptive fields, a signature inherited by downstream neurons and implicated in color signaling. In the peripheral retina, the functional connectivity of cone inputs to the circuitry that mediates lateral inhibition is not cone-type specific, but whether these wiring schemes are maintained closer to the fovea remains unsettled, in part because central retinal anatomy is not easily amenable to direct physiological assessment. Here, we demonstrate how the precise topography of the long (L)-, middle (M)-, and short (S)-wavelength-sensitive cones in the human parafovea (1.5° eccentricity) shapes perceptual sensitivity. We used adaptive optics microstimulation to measure psychophysical detection thresholds from individual cones with spectral types that had been classified independently by absorptance imaging. Measured against chromatic adapting backgrounds, the sensitivities of L and M cones were, on average, receptor-type specific, but individual cone thresholds varied systematically with the number of preferentially activated cones in the immediate neighborhood. The spatial and spectral patterns of these interactions suggest that interneurons mediating lateral inhibition in the central retina, likely horizontal cells, establish functional connections with L and M cones indiscriminately, implying that the cone-selective circuitry supporting red-green color vision emerges after the first retinal synapse.SIGNIFICANCE STATEMENT We present evidence for spatially antagonistic interactions between individual, spectrally typed cones in the central retina of human observers using adaptive optics. Using chromatic adapting fields to modulate the relative steady-state activity of long (L)- and middle (M)-wavelength-sensitive cones, we found that single-cone detection thresholds varied predictably with the spectral demographics of the surrounding cones. The spatial scale and spectral pattern of these photoreceptor interactions were consistent with lateral inhibition mediated by retinal horizontal cells that receive nonselective input from L and M cones. These results demonstrate a clear link between the neural architecture of the visual system inputs-cone photoreceptors-and visual perception and have implications for the neural locus of the cone-specific circuitry supporting color vision.

Normal Perceptual Sensitivity Arising From Weakly Reflective Cone Photoreceptors.

To determine the light sensitivity of poorly reflective cones observed in retinas of normal subjects, and to establish a relationship between cone reflectivity and perceptual threshold. Five subjects (four male, one female) with normal vision were imaged longitudinally (7-26 imaging sessions, representing 82-896 days) using adaptive optics scanning laser ophthalmoscopy (AOSLO) to monitor cone reflectance. Ten cones with unusually low reflectivity, as well as 10 normally reflective cones serving as controls, were targeted for perceptual testing. Cone-sized stimuli were delivered to the targeted cones and luminance increment thresholds were quantified. Thresholds were measured three to five times per session for each cone in the 10 pairs, all located 2.2 to 3.3° from the center of gaze. Compared with other cones in the same retinal area, three of 10 monitored dark cones were persistently poorly reflective, while seven occasionally manifested normal reflectance. Tested psychophysically, all 10 dark cones had thresholds comparable with those from normally reflecting cones measured concurrently (P = 0.49). The variation observed in dark cone thresholds also matched the wide variation seen in a large population (n = 56 cone pairs, six subjects) of normal cones; in the latter, no correlation was found between cone reflectivity and threshold (P = 0.0502). Low cone reflectance cannot be used as a reliable indicator of cone sensitivity to light in normal retinas. To improve assessment of early retinal pathology, other diagnostic criteria should be employed along with imaging and cone-based microperimetry.

PSYCHOPHYSICAL MEASUREMENT OF ROD AND CONE THRESHOLDS IN STARGARDT DISEASE WITH FULL-FIELD STIMULI

To investigate psychophysical thresholds in Stargardt disease with the full-field stimulus test (FST). Visual acuity, spectral domain optical coherence tomography, full-field electroretinogram, and FST measurements were made in 1 eye of 24 patients with Stargardt disease. Dark-adapted rod FST thresholds were measured with short-wavelength stimuli, and cone FST thresholds were obtained from the cone plateau phase of dark adaptation using long-wavelength stimuli. Correlation coefficients were calculated for FST thresholds versus macular thickness, visual acuity, and electroretinogram amplitudes. The Stargardt disease patients' FST cone thresholds correlated significantly with visual acuity, macular thickness, and electroretinogram cone response amplitudes (all P < 0.01). The patients' FST rod thresholds correlated with electroretinogram rod response amplitudes (P < 0.01) but not macular thickness (P = 0.05). All patients with Stargardt disease with flecks confined to the macula, and most of the patients with flecks extending outside of the macula had normal FST thresholds. All patients with extramacular atrophic changes had elevated FST cone thresholds and most had elevated FST rod thresholds. Full-field stimulus test rod and cone threshold elevation in patients with Stargardt disease correlated well with measures of structure and function, as well as ophthalmoscopic retinal appearance. The Full-field stimulus test appears to be a useful tool for assessing rod and cone function in Stargardt disease.

The association between dark adaptation and macular pigment optical density in healthy subjects

To investigate whether macular pigment optical density (MPOD) is related to dark adaptation in healthy subjects. Dark adaptation was measured after a minimum 30 % pigment bleach in 33 subjects (aged 15-68), using a white 1° stimulus presented 11° below fixation on a cathode ray tube monitor. The luminance range of the monitor was extended using neutral density filters. A heterochromatic flicker photometry based instrument (MPS 9000) was used to measure MPOD. The average MPOD for the whole group was 0.37 ± 0.21 optical density units. Subjects with lighter irides had on average 40 % lower MPOD compared to those with darker irides (0.3 ± 0.20 vs 0.5 ± 0.19). Group mean MPOD was weakly associated with second (r = 0.32, p = 0.07) and third rod-mediated recovery rates (r = 0.31, p = 0.08) and with the rod threshold (r = -0.24, p = 0.18) 30 min after the onset of bleach. MPOD was unrelated to cone time constant (r = -0.02, p = 0.91), cone threshold (r = -0.01, p = 0.96), rod-cone break (r = 0.13, p = 0.45) or the rod-rod break (r = 0.11, p = 0.52). The second rod-mediated recovery rate (S2) for the lower 10th percentile of MPOD (n = 4) was 0.18 log cd.m(-2).min(-1) and 0.24 log cd.m(-2).min(-1) for the upper 10th percentile (n = 4). The two groups were significantly different (t = -2.67, p = 0.037). We report a statistically significant difference between subjects falling in the 10th percentile extremes of MPOD and rod-mediated but not cone-mediated sensitivity recovery. Further investigation into the relationship between MPOD and rod function is warranted, particularly extending the work to encompass those with low MPOD and poor night vision.